Interferons are glycoproteins whose synthesis is induced in various animal cells upon infection by any of a large variety of viruses. They are released from the producing cells, are attached to other cells, and impair in these the replication of a large variety of viruses. We are studying the molecular basis of this impairment. Many of our studies are performed with mouse Ehrlich ascites tumor cells, mouse L fibroblasts, and reovirus, a virus with a segmented, double-stranded RNA genome. Recently, we observed several differences in biochemical characteristics between extracts from interferon-treated cells (S30INT) and those from untreated cells (S30C): 1) The methylation of viral mRNA is impaired in S30INT. 2) Viral mRNA is degraded faster in S30INT than in S30C, but only if the extracts are supplemented with double-stranded RNA and ATP. 3) Double-stranded RNA promotes the phosphorylation by ATP or at least two proteins in S30INT and only to a much lesser extent in S30C. The molecular basis of these phenomena and their relevance to the inhibition of virus replication in interferon-treated cells will be examined.